全雄激素阻断治疗抑制人前列腺癌前列腺干细胞抗原mRNA的表达

Complete androgen ablation suppresses prostate stem cell antigen mRNA expression in human prostate carcinoma

目的观察全雄激素阻断（CAA）治疗前后前列腺干细胞抗原（PSCA）mRNA 表达水平的变化,并进一步评估 PSCA 在人前列腺癌的临床预后价值。方法对42例男性患者的前列腺活检组织或经尿道前列腺切除组织（包括去势前局限性前列腺癌组织和前列腺癌根治术前接受比卡鲁胺和醋酸戈舍瑞林去势治疗3个月后的癌组织）进行原位杂交。PSCA mRNA 的肿瘤细胞质染色结果由两位病理学专家独立评估,t 检验分析 CAA 前后 PSCA mRNA 表达水平的差异。前列腺癌根治术后进行36~40个月的随访,旨在评估 PSCA mRNA 表达水平与癌症局部复发或转移的相关性。结果原位杂交标记 PSCA mRNA 阳性的细胞由 CAA 前的67.3%（0~89%）±9.4%下降到 CAA 后33.8%（0~92%）±7.7%（P 〈0.001）。CAA 前95.2%（40/42）的患者 PSCA mRNA 表达阳性,而去势后阳性率降到67.5%（27/40）,且随访未发现有局部复发或远处转移。PSCA mRNA 阳性表达的减少取决于原始肿瘤的 Gleason 评分,Gleason≤6：19.3%±4.7%；Gleason=7：38.8%±7.2%；Gleason≥8：73.4%±13.8%（P 〈0.05）。其余13例,CAA 后 PSCA mRNA 阳性表达水平增加,且随访发现3例有局限复发,4例有远处转移。结论前列腺癌 CAA 可抑制 PSCA mRNA 的表达；去势治疗后 PSCA mRNA 表达的增加可成为肿瘤复发或远处转移的一个不利预测指标。

Objective The purpose of the present study was to investigate the variations in the ex-pression levels of prostate stem cell antigen （PSCA）mRNA before and after complete androgen ablation （CAA）,and further evaluate the clinically prognostic value of PSCA in human prostate carcinoma. Meth-ods PSCA in situ hybridization （ISH）was performed on the cancerous pretreatment biopsy or transure-thral resection of prostate tissue of 42 men with primarily organ-confined prostate cancer before CAA,and on their tumor tissue from radical retropubic prostatectomy after CAA with bicalutamide and goserelin ace-tate for 3 months prior to undergoing radical prostatectomy.Tumor cytoplasmic staining of PSCA mRNA was evaluated by two independent pathologists and the differences of PSCA mRNA expression levels between the samples before and after CAA were analyzed using the Student＆#39;s t-test.Thirty-six to forty months follow-up studies after radical retropubic prostatectomy were performed and aimed at assessing the correlation of PSCA mRNA expression level with local recurrences or metastases from the cancer. Results The percent of cells positive for PSCA mRNA by ISH labeling declined from 67.3% （0-89%）±9.4% before CAA to 33.8% （0-92%）±7.7% after CAA （P 〈0.001 ）.Before CAA,40 of 42 cases （95.2%）were positive for PSCA mRNA labeling,however,after CAA the percentage of positive reactivity of PSCA mRNA was decreased to 27 of 40 cases （67.5%）,in which none was found with local recurrences or distant metastases after radical prostatectomy on follow-up .＆amp;nbsp;This decline in PSCA mRNA labeling was dependent on the original tumor grade with Gleason score of ≤6：1 9.3%±4.7%, Gleason score of 7：38.8%±7.2%,and a Gleason score of ≥8：73.4%±13.8% （P 〈0.05,respectively）.The rest 13 cases had the increased percentage of cells positive for PSCA mRNA after CAA,in which 3 cases were found with local recurrences and 4 ca-ses with distant metastases from tumor on follow-up. Conclusions Our data demonstrate that CAA for prostate cancer can sup-press PSCA mRNA expression with a tumor grade dependence and the increased expression of PSCA mRNA after CAA may be a clinically adverse predictor for tumor recurrences or distant metastases.